Hepatocyte growth factor protects mice against anti-Fas antibody-induced death

We have studied the efficacy of hepatocyte growth factor (HGF) in preventin g anti-Fas antibody-induced hepatic apoptosis in mice and the resulting sev ere liver damage and death. HGF was intravenously administered at a dose of 500 mu g/kg to mice intraperitoneally injected with 6.7 or 10 mu g of anti -Fas monoclonal antibody, Jo2. Repeated administration of HGF dramatically prevented the death of mice induced by Jo2. HGF also diminished increases i n both alanine transaminase and aspartate transaminase activity as well as total and direct bilirubin levels in line with histological findings of pro gressive improvement of the damaged liver. A single administration of HGF 1 h before Jo2 injection rescued the mice from death. A single administratio n of epidermal growth factor(ECF) mimicked HGF action in Jo2-injected mice, whereas neither growth hormone nor insulin-like growth factor-1 prevented death. These findings indicate that HGF or EGF effectively blocks death sig nalling pathways activated by the Fas and Fas ligand interaction. Med Sci R es 27:355-359 (C) 1999 Lippincott Williams & Wilkins.